Knowledge of the function of the diseased human nephron is based upon indirect clearance type studies. The proposed studies will examine isolated nephron segments from nephrectomized, diseased kidneys by means of in vitro perfusion. Comparisons will be made with the function of normal nephron segments derived from the intact parenchyma of kidneys removed in the treatment of renal carcinomas. Preoperative clinical evaluation of renal function will allow correlations to be drawn between in vivo and in vitro function. The nature of the various disease states will also be defined histologically. In all segments studied basic measurements will include net volume reabsorption, transepithelial potential difference, tubular geometry and dry weight per unit length. Specific studies will investigate aspects of hormone responsiveness and transport functions of "uremic" nephrons. (1) The response of the cortical collecting tubule (CCT) to vasopressin will be studied by comparing net water flux, osmotic water permeability and adenylate cyclase activity in normal and diseased CCTS. (2) The response of the proximal convoluted tubule (PCT) to parathyroid hormone and the relationships between volume and phosphate reabsorption in the hypertrophied PCT will be studied. (3) The capacity of the proximal straight tubule (PST) to secrete organic anions and the influence of this process on net fluid transport will be evaluated. (4) The characteristics of potassium transport by the CCT in uremia will be correlated with Na-K ATPase activity in the same segment in an attempt to establish whether a definitive association underlies the phenomenon of potassium adaptation in uremia.